According to the dopamine hypothesis of schizophrenia, there is an excess of dopamine in the mesolimbic pathway (nucleus accumbens), and this contributes to the positive symptoms of schizophrenia.
I am not sure what the cause of anhedonia (reduced interest), one of the negative symptom of schizophrenia. If nucleus accumbens plays a role in the reward system and there is an excess of dopamine, isn't it the case that there should be an increase in interest, that is, no anhedonia?
The dopamine hypothesis includes brain regions with reduced dopamine transmission as well. The prefrontal cortex in specific has reduced dopaminergic activity and is implicated in anhedonia. It affects pleasure seeking behavior through interactions with the nucleus accumbens.
The negative symptoms of schizophrenia are less well understood as the positive counterparts. One thing is for sure, the dopamine hypothesis cannot explain everything. It is a very useful working hypothesis, but primarily based on the first generation antipsychotics such as haloperidol with mainly dopaminergic mechanisms of action. In turn, these drugs mainly and effectively target the positive symptomatology (excessive dopaminergic transmission).
Second-generation antipsychotics are more effective in treating the negative symptoms and are thought to actually increase cortical dopamine, as well as and acetylcholine release, as well as have a variety of effects on the glutamatergic system not shared by the typical agents first-generation antipsychotics (Meltzer, 2004).
In fact, the dopamine hypothesis has been improved and adjusted during decades of intensive research. One of the important things that has come out of this is that dopamine neurotransmission is regionally affected, with a prefrontal hypodopaminergia (prefrontal cortex, or PFC and a subcortical hyperdopaminergia (e.g. in the pleasure centers). An excellent review of the historic developments in the dopamine hypothesis was published by Howes & Kapur (2009)
Now on to anhedonia. Pleasure perception per se seems largely unaffected in schizophrenic people, it is the anticipation of pleasure that seems negatively affected. This is accompanied by reduced motivation and goal-directed actions to seek pleasure. Anhedonia is primarily attributed to disturbed interactions between the ventral (nucleus accumbens) and dorsal striatum (mainly the caudate) and the PFC and not so much in the experience of pleasure per se. In addition, insular cortex, amgydala and hippocampus may be involved. A dysfunctional coupling between the anterior cingulate and the insular cortex (the “salience network”) has also been linked to the failure to appropriately process reward in schizophrenia. Lastly, goal-directed actions needed to obtain the reward and dependent on the PFC is dependent on not only dopaminergic, but also adrenergic and other mechanisms. This is all nutshelled information and I would encourage you to read Milan et al. (2014), who have written an extensive and excellent review focusing on anhedonia in specific as a negative symptom. Fig. 1 is obtained from that paper and shows the complexity of anhedonia.
Fig. 1. Cerebral circuits involved in negative symptoms, with a focus on deficits in anticipatory reward. source: Milan et al. (2014)
- Hows & Kapur, Schizophr Bull (2009); 35(3): 549-62
- Meltzer, Curr Opin Pharmacol (2004); 4(1): 53-7
- Milan et al., Eur Neuropsychopharmacol (2014)24(5): 645-92
High Dopamine Levels: Symptoms & Adverse Reactions
Most people have heard of the neurotransmitter dopamine and understand that it’s release is associated with feelings of pleasure and reward. Dopamine functions as a neurotransmitter that plays a major role in reward and motivation behavior. Most rewards such as: food, sex, drugs, etc. are all capable of increasing the level of dopamine in the brain. Just before an orgasm, dopamine levels are considered at their “peak.”
In addition to playing an integral role in motivational and reward processes, dopamine is involved in motor control as well as triggering a release of various hormones. High levels of dopamine tend to enhance concentration, boost mood, and have a pro-social effect. Anyone that’s taken a psychostimulant medication like Adderall has gotten a first-hand experience of the psychological outcome of elevated dopamine.
Within the body, dopamine widens the blood vessels, by inhibiting norepinephrine release. It also helps us excrete sodium and is able to reduce levels of insulin. Dopamine also serves to protect your gastrointestinal tract and improves immune function. While maintaining sufficient dopamine levels is beneficial for mental health and physical functioning, too much dopamine can create dysfunction.
Cocaine harms brain's 'pleasure center,' addict study finds
ANN ARBOR, MI - New research results strongly suggest that cocaine bites the hand that feeds it, in essence, by harming or even killing the very brain cells that trigger the "high" that cocaine users feel.
This first-ever direct finding of cocaine-induced damage to key cells in the human brain's dopamine "pleasure center" may help explain many aspects of cocaine addiction, and perhaps aid the development of anti-addiction drugs. It also could help scientists understand other disorders involving the same brain cells, including depression.
The results are the latest from research involving postmortem brain tissue samples from cocaine abusers and control subjects, performed at the University of Michigan Health System and the VA Ann Arbor Healthcare System. The paper will appear in the January issue of the American Journal of Psychiatry.
"This is the clearest evidence to date that the specific neurons cocaine interacts with don't like it and are disturbed by the drug's effects," says Karley Little, M.D., associate professor of psychiatry at the U-M Medical School and chief of the VAHS Affective Neuropharmacology Laboratory. "The questions we now face are: Are the cells dormant or damaged, is the effect reversible or permanent, and is it preventable?"
Little and his colleagues report results from 35 known cocaine abusers and 35 non-drug users of about the same age, sex, race and causes of death. Using brain samples normally removed during autopsy, the researchers measured several indicators of the health of the subjects' dopamine brain cells, which release a pleasure-signaling chemical called dopamine. The cells interact directly with cocaine.
The team looked at levels of a protein called VMAT2, as well as VMAT2's binding to a selective radiotracer molecule, and overall dopamine level.
In all three, cocaine users' levels were significantly lower than control subjects. Levels tended to be lowest in cocaine users with depression.
The paper gives the most conclusive evidence yet that dopamine neurons are harmed by cocaine use, because it uses three molecular measures that provide a trustworthy assessment of dopamine neuron health.
Dopamine, Little explains, triggers the actions required to repeat previous pleasures. It's not only involved in drug users' "high" - it helps drive us to eat, work, feel emotions, and reproduce. Normally, when something pleasurable happens, dopamine neurons pump the chemical into the gaps between themselves and related brain cells. Dopamine finds its way to receptors on neighboring cells, triggering signals that help set off pathways to different feelings or sensations.
Then, the dopamine is normally brought back into its home cell, entering through a gateway in the membrane called a transporter. While our brain waits for another pleasurable stimulus - a good meal, a smile from a friend, a kiss - dopamine lies waiting inside the neuron, sequestered in tiny packets called vesicles. VMAT2 acts as a pump to pull returning dopamine into vesicles.
When it comes time for another dopamine release, the vesicles merge with the cell membrane, dumping their contents into the gap, or synapse, and the pleasure signaling process begins again.
Dopamine neurons in the brain's pleasure center die off at a steady rate over a person's lifetime. Severe damage is a hallmark of Parkinson's disease, causing its loss of movement control. "As the words themselves suggest, there's an intimate connection between motion and emotion," says Little. "Emotion puts you in motion -- they're pre-activity preparations. It's not surprising that the basal ganglia, where these dopamine neurons are, is very active in 'emotional states.'"
When first taken, cocaine has a disruptive effect on the brain's dopamine system: It blocks the transporters that return dopamine to its home cell once its signaling job is done. With nowhere to go, dopamine builds up in the synapse and keeps binding with other cells' receptors, sending pleasure signals over and over again. This helps cause the intense "high" cocaine users feel.
Since the dopamine system helps us recognize pleasurable experiences and seek to repeat them, cocaine's long-term dopamine effects likely contribute to the craving addicts feel, and the decreased motivation, stunted emotion and uncomfortable withdrawal they face.
In recent years, many researchers have come to suspect that chronic cocaine use causes the brain to adapt to the drug's presence by altering the molecules involved in dopamine release and reuptake, and in the genetic instructions needed to make those molecules. Little and his colleagues are studying the effects of long-term cocaine use on the brain at a molecular level, in an attempt to explain the effects seen in cocaine users and addicts.
In several studies, including the current one, they've used postmortem samples of brain tissue from known cocaine users who were using the drug at the time of their deaths, and from well-matched control subjects. They focused in on the striatum, an area of the brain with the highest concentration of dopamine neurons.
With approval from the U-M Institutional Review Board and appropriate consent, they interviewed relatives and friends of the subjects, and asked about the subjects' alcohol use, mental illness and other characteristics.
The team previously showed that cocaine users have higher numbers of dopamine transporters, suggesting that the cells tried to make more return gateways to compensate for blocked ones. Recently, they showed in cell cultures that cocaine causes more dopamine transporters to travel from the interior of a cell to the membrane, increasing the overall dopamine uptake level.
The data provide support for the idea that chronic cocaine abuse leads to a phenomenon seen in animals, called allostasis of reward. With extended use of cocaine, the brain's response to the drug is "reset", and drug-taking once pursued for the pleasure it caused becomes drug-taking to avoid the negative feelings associated with the absence of cocaine.
The new data suggest this same phenomenon occurs in human cocaine users, and is quite pronounced at the neurochemical level. The experiment sheds light on the molecular mechanisms involved as dopamine-producing brain cells try to adapt to a cocaine-drenched environment.
VMAT2 protein levels, measured through the use of specific antibodies that bind to the protein, are not as affected by other factors as dopamine transporters are. VMAT2 binding availability, measured through a unique radioactive tracer developed by U-M nuclear medicine specialists, is another assessment of VMAT2 presence and activity. And the overall dopamine level, measured through liquid chromatography, shows how much of the chemical was available at the time of death.
On the whole, all three were significantly lower in cocaine users than in non-drug users. A history of alcohol abuse in cocaine users or controls did not affect the difference significantly.
Levels of VMAT2 protein were lowest in the seven cocaine users with mood disorders that may have been caused by cocaine use. Researchers have found that depressed cocaine users have more severe addiction and mental health problems than non-depressed users. Little hypothesizes that the decreased dopamine vesicles and increased transporters may contribute to cocaine-induced depression and other depressive disorders. This may explain why depressed cocaine users are less likely to respond to some depression treatments.
In all, Little says, "We could be seeing the result of the brain's attempt to regulate the dopamine system in response to cocaine use, to try to reduce the amount of dopamine that's released by reducing the ability to collect it in vesicles. But we could also be seeing real damage or death to dopamine neurons. Either way, this highlights the fragility of these neurons and shows the vicious cycle that cocaine use can create." New treatments will have to break that cycle, he adds, and the new findings may help steer clinical researchers.
He also emphasizes that the vulnerable nature of dopamine neurons is important in understanding the moods and actions of normal adults as they age and lose dopamine neurons naturally. Considerable evidence suggests that uncontained dopamine may be mildly toxic over time.
In future research, Little and his colleagues hope to look for differences in the number of dopamine neurons in the subjects' brain samples, and to study gene activity in the cells of cocaine users and control subjects. They also hope their results will help other researchers study living cocaine users and look for signs of decreased VMAT2 levels.
In addition to Little, the study's authors are David Krolewski, M.S. Lian Zhang, Ph.D. and Bader Cassin, M.D. U-M nuclear medicine researcher Kirk Frey, M.D., led the team that developed the radioactive tracer used to measure VMAT2 binding levels. The study was funded by the National Institute on Drug Abuse of the National Institutes of Health, and by a VA Merit Award.
Reference: American Journal of Psychiatry 160:1-9, January 2003.
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Serotonin And Drug Abuse
Ever wonder why you have those strange dreams about standing in front of your biology class in nothing but a transparent tunic? Insecurities and unresolved issues appear to manifest during REM sleep, a time when mood-regulating serotonin is taking its turn to rest. At about the time an elf brandishing a giant carrot ride in atop a pink unicorn, serotonin neurotransmission has ceased. Taking a drug like LSD, which inhibits the release of serotonin, can generate similar effects during periods of wakefulness, with those giant carrot-wielding elves showing up at your front door.
BioBases Chapter 16
Schizophrenia is a serious disorder only in adulthood.
The incidence of schizophrenia is about 10 percent of the world population.
The term means "split mind."
Schizophrenia is largely diagnosed in childhood.
Females are more likely to experience schizophrenia.
Schizophrenia results from brain damage and resultant excesses in dopamine release.
a split that occurs between the individual and reality.
multiple personalities in one individual.
becoming two separate individuals that do not realize the existence of the other individual.
flattened emotional response.
hallucinations and social withdrawal.
delusions and hallucinations.
positive symptoms and negative symptoms.
are linked to brain damage.
are perceptions that occur without the presence of stimuli.
indicate the presence of depression.
represent additions to normal behaviors.
are likely to be caused by excessive brain dopamine activity.
represent the absence of normal behaviors.
usually require long hospital terms to treat.
are associated with low levels of brain dopamine activity.
indicate that the patient cannot accurately perceive reality.
experiencing a feeling of euphoria at the start of an episode.
exhibiting excessive emotional expression.
thinking that you are the most powerful being on earth.
schizophrenic parents rarely marry.
schizophrenia is not produced by a single gene.
schizophrenia is produced by a single dominant gene.
has abstained from drugs and alcohol.
smokes marijuana, but does not use alcohol.
the concordance rate for schizophrenia is lower for monozygotic than dizygotic twins.
adoption studies indicate a biological basis for schizophrenia.
several genes may be involved in schizophrenia.
ventricular size dichorionic
are more likely to develop schizophrenia if they are born between February and May.
are more likely to be diagnosed with schizophrenia between February and May.
with schizophrenia are more likely to demonstrate symptoms during winter months.
a fetus born during the late summer is more likely to have experienced a viral infection during the second trimester.
immune function is generally enhanced during the winter months.
a fetus born in late winter may be exposed to a viral infection during the second trimester.
mothers taking antibiotics should be unlikely to have schizophrenic offspring.
children born a few months before a flu outbreak are more likely to develop schizophrenia.
exposure of the fetus to a virus during the third trimester is most likely to induce schizophrenia.
mothers taking antibiotics are unlikely to have schizophrenic offspring.
analysis of stored serum from mothers whose children later developed schizophrenia showed evidence of maternal infection.
exposure of the fetus to a virus during the third trimester is most likely to induce schizophrenia.
The seasonality effect rarely occurs in rural settings.
The seasonality effect is mostly due to indoor smoking by the mother during the winter.
The seasonality effect is enhanced when fall temperatures are higher than normal.
The Dopamine Hypothesis of Schizophrenia – Advances in Neurobiology and Clinical Application
The dopamine hypothesis stems from early research carried out in the 1960’s and 1970’s when studies involved the use of amphetamine (increases dopamine levels) which increased psychotic symptoms while reserpine which depletes dopamine levels reduced psychotic symptoms.
The original dopamine hypothesis was put forward by Van Rossum in 1967 that stated that there was hyperactivity of dopamine transmission, which resulted in symptoms of schizophrenia and drugs that blocked dopamine reduced psychotic symptoms. 
DOPAMINE PRODUCTION AND METABOLISM
Dopamine is synthesised from the amino acid tyrosine. Tyrosine is converted into DOPA by the enzyme tyrosine hydroxylase.
DOPA is converted into dopamine (DA) by the enzyme DOPA decarboxylase (DOPADC).
This dopamine is packed and stored into synaptic vesicles via the vesicular monoamine transporter (VMAT2) and stored until its release into the synapse.
When dopamine is released during neurotransmission, it acts on 5 types of postsynaptic receptors (D1-D5).
A negative feedback mechanism exists through the presynaptic D2 receptor which regulates the release of dopamine from the presynaptic neuron.
Any excess dopamine is also ‘mopped up’ from the synapse by Dopamine transporter (DAT) and stored in the vesicles via VMAT2.
Dopamine is broken down by monoamine oxidase A (MAO-A), MAO-B and catechol-o-methyltransferase (COMT).
- Tyrosine hydroxylase is the rate-limiting step in the production of dopamine. Its expression is significantly increased in the substantia nigra of schizophrenia patients when compared to normal healthy subjects. 
- Carbidopa is a peripheral DOPA-decarboxylase inhibitor co-administered with levodopa. Carbidopa prevents the conversion of levodopa to dopamine in the periphery, thus allowing more levodopa to pass the blood-brain barrier to be converted into dopamine for its therapeutic effect.
- Methamphetamine increases extracellular dopamine by interacting at vesicular monoamine transporter-2 (VMAT2) to inhibit dopamine uptake and promote dopamine release from synaptic vesicles, increasing cytosolic dopamine available for reverse transport by the dopamine transporter (DAT).
- Valbenazine a highly selective VMAT2 inhibitor has been approved by the FDA for the treatment of tardive dyskinesia.
- There is compelling evidence that presynaptic dopamine dysfunction results in increased availability and release of dopamine and this has been shown to be associated with prodromal symptoms of schizophrenia. Furthermore, dopamine synthesis capacity has also been shown to steadily increase with the onset of severe psychotic symptoms. 
- Dopaminergic transmission in the prefrontal cortex is mainly mediated by D1 receptors, and D1 dysfunction has been linked to cognitive impairment and negative symptoms of schizophrenia. 
THE 4 DOPAMINE PATHWAYS IN THE BRAIN
1.The Mesolimbic Pathway
- The pathway projects from the ventral tegmental area (VTA) to the nucleus accumbens in the limbic system.
- Hyperactivity of dopamine in the mesolimbic pathway mediates positive psychotic symptoms. The pathway may also mediate aggression.
- The mesolimbic pathway is also the site of the rewards pathway and mediates pleasure and reward. Antipsychotics can block D2 receptors in this pathway reducing pleasure effects. This may be one explanation as to why individuals with schizophrenia have a higher incidence of smoking as nicotine enhances dopamine in the reward pathway (self-medication hypothesis)
- Antagonism of D2 receptors in the mesolimbic pathway treats positive psychotic symptoms.
- There is an occupancy requirement with the minimum threshold at 65% occupancy for treatment to be effective. Observations support this relationship between D2-receptor occupancy and clinical response that 80% of responders have D2-receptor occupancy above this threshold after treatment. 
2.The Mesocortical Pathway
- Projects from the VTA to the prefrontal cortex.
- Projections to the dorsolateral prefrontal cortex regulate cognition and executive functioning.
- Projections into the ventromedial prefrontal cortex regulate emotions and affect.
- Decreased dopamine in the mesocortical projection to the dorsolateral prefrontal cortex is postulated to be responsible for negative and depressive symptoms of schizophrenia.
- Nicotine releases dopamine in the mesocortical pathways alleviating negative symptoms (self-medication hypothesis).
3.The Nigrostriatal Pathway
- Projects from the dopaminergic neurons in the substantia nigra to the basal ganglia or striatum.
- The nigrostriatal pathway mediates motor movements.
- Blockade of dopamine D2 receptors in this pathway can lead to dystonia, parkinsonian symptoms and akathisia.
- Hyperactivity of dopamine in the nigrostriatal pathway is the postulated mechanism in hyperkinetic movement disorders such as chorea, tics and dyskinesias.
- Long-standing D2 blockade in the nigrostriatal pathway can lead to tardive dyskinesia.
4.The Tuberoinfundibular (TI) Pathway
- Projects from the hypothalamus to the anterior pituitary.
- The TI pathway inhibits prolactin release.
- Blockade of D2 receptors in this pathway can lead to hyperprolactinemia which clinically manifests as amenorrhoea, galactorrhoea and sexual dysfunction.
- Long-term hyperprolactinemia can be associated with osteoporosis.
Conceptualisation of Schizophrenia
Based on the above understanding, schizophrenia is best conceptualised as a complex entity which involves multiple pathways.
In clinical practice, there can be a disproportionate focus on positive psychotic symptoms.
It is however, important to recognise that affective (e.g depressive), negative and cognitive symptoms are a core part of schizophrenia and should be taken into account in treatment.
The aim of treatment, thus, is to modulate treatment creating a balance between effectiveness and reduction of side effects.
The balance is achieved by optimal dopamine blockade in the mesolimbic pathway while preserving (or enhancing) dopamine transmission in the other pathways.
DOPAMINE AND SCHIZOPHRENIA
The dopamine hypothesis of schizophrenia has moved from the dopamine receptor hypothesis (increased dopamine transmission at the postsynaptic receptors) to a focus on presynaptic striatal hyperdopaminergia.
According to Howes and Kapur-
This hypothesis accounts for the multiple environmental and genetic risk factors for schizophrenia and proposes that these interact to funnel through one final common pathway of presynaptic striatal hyperdopaminergia.
In addition to funneling through dopamine dysregulation, the multiple environmental and genetic risk factors influence diagnosis by affecting other aspects of brain function that underlie negative and cognitive symptoms. Schizophrenia is thus dopamine dysregulation in the context of a compromised brain. 
The hypothesis that the final common pathway is presynaptic dopamine dysregulation has some important clinical implications. Firstly, it implies that current antipsychotic drugs are not treating the primary abnormality and are acting downstream. While antipsychotic drugs block the effect of inappropriate dopamine release, they may paradoxically worsen the primary abnormality by blocking presynaptic D2 autoreceptors, resulting in a compensatory increase in dopamine synthesis.
This may explain why patients relapse rapidly on stopping their medication, and if the drugs may even worsen the primary abnormality, it also accounts for more severe relapse after discontinuing treatment. This suggests that drug development needs to focus on modulating presynaptic striatal dopamine function, either directly or through upstream effects. 
Concept of Salience
Usually, dopamine’s role is to mediate motivational salience and thereby gives a person the ability to determine what stimulus grabs their attention and drives the subsequent behaviour.
Schizophrenia is associated with an aberrant attribution of salience due to dysregulated striatal dopamine transmission.
Dysregulation of the dopamine system ultimately leads to irrelevant stimuli becoming more prominent which provides a basis for psychotic phenomena such as ideas of reference, where everyday occurrences may be layered with a with a heightened sense of bizarre significance. Furthermore, this misattribution of salience can lead to paranoid behaviour and persecutory delusions. 
LIMITATIONS OF THE DOPAMINE HYPOTHESIS OF SCHIZOPHRENIA
Current research shows that one-third of individuals with schizophrenia do not respond to non-clozapine antipsychotics despite high levels of D2-receptor occupancy.
Furthermore, a study using tetrabenazine (used as augmentation) which depletes presynaptic dopamine was not found to be effective in augmenting a clinical response in schizophrenia. 
Therefore, for a significant number of patients with schizophrenia, the basis of their symptoms is either unrelated to dopaminergic dysfunction or is associated with something more than just dopamine excess.
Alternatively, this could also mean that for some patients with schizophrenia there might be a non-dopaminergic sub-type of schizophrenia.
The current dopamine hypothesis of schizophrenia does not adequately explain the cognitive and negative symptoms. Current treatments which modulate dopamine transmission have only modest effects in improving these symptoms.
It has taken two decades for the dopamine hypothesis to evolve and reach its current state. More recent evidence shows another neurotransmitter, glutamate playing an essential role in schizophrenia.
The future likely holds a lot more secrets about schizophrenia which should unravel with the advances in understanding the brain.
Chapter 14 - Schizophrenia
Various psychotic symptoms, such as delusions, hallucinations, disorganized speech, restricted or inappropriate affect, and catatonia.
Lifetime prevalence: 1.0%
Duration: 6 months or more.
Both genders are affected equally. Average onset is 23 years for men and 28 years for women.
1. For 1 month, individual displays two or more of the following symptoms much of the time:
(c) Disorganized speech
(d) Very abnormal motor activity, including catatonia
(e) Negative symptoms
2. At least one of the individual's symptoms must be delusions, hallucinations, or disorganized speech.
3. Individual functions much more poorly in various life spheres than was the case prior to the symptoms.
4. Beyond this 1 month of intense symptomology, individual continues to display some degree of impaired functioning for at least 5 additional months.
The hallmark of schizophrenia. A significant loss of contact with reality.
Their ability to perceive and respond to the environment becomes so disturbed that they may not be able to function at home, with friends, in school, or at work.
They may have hallucinations (false sensory perceptions) or delusions (false beliefs), or they may withdraw into a private world.
Substances combined with a mental disorder can produce a pattern of severe psychosis. When substances are out of reach, the patients typically calm down, become more coherent, and are treatment ready in the community.
Tend to be young, male, and between 20-50% of all people with chronic mental disorders may be MICAs.
They often rate below average in social functioning, school achievement, and above average in poverty, acting-out behaviour, emergency room visits, and crime.
Cocaine and amphetamines exacerbate the symptoms of psychosis and can quickly intensify the symptoms of schizophrenia.
The treatment of MICAs is further complicated by the fact that many treatment facilities are designed and funded to treat either mental disorders or substance abuse only some are equipped or willing to treat both. As a result, it is not uncommon for MICA patients to be rejected as inappropriate for treatment in both substance abuse and mental health programs.
Many such patients fall through the cracks in this way and find themselves in jail or homeless shelters.
Negative symptoms (deficits of thought, emotion, and behavior).
They are "pathological excesses," or bizarre additions, to a person's behavior.
A false belief that is firmly maintained in spite of incontrovertible and obvious proof to the contrary.
Ideas they believe wholeheartedly but that have no basis in fact. The deluded person may consider the ideas enlightening or may feel confused by them. Some people hold a single delusion that dominates their lives and behavior others have many delusions.
Delusions of persecution, reference, control and grandeur (thought broadcasting, thought insertion, and thought withdrawal).
People with such delusions believe they are being plotted or discriminated against, spied on, slandered, threatened, attacked, conspired against, or deliberately victimized.
They might believe neutral comments carry personal messages directed at them and can come in negative forms. These communications might come from TV, radio, people on the street. The messages might also come from objects or events with no basis in reality.
People with schizophrenia may not be able to think logically and may speak in peculiar ways.
They can cause the sufferer great confusion and make communication extremely difficult.
It has been documented in studies that people with schizophrenia have issues with perception and sensory stimuli. They have trouble focusing on one sound when there are multiple noises and sounds accompanying it.
They also have demonstrated deficiencies in smooth pursuit eye movements indicating a weakness that can be related to attention problems.
Can occur in any sensory modality. Seems real but occurs in absence of any external perceptual stimulus. Possible causes are:
-Disturbances in brain chemistry - neurotransmitter dopamine. Drugs that lead to dopamine production such as cocaine (which can induce them).
-Auditory may be a form of inner speech that for unknown reasons because attributed to external sources rather than to one's own thoughts.
One line of research measured blood flow in Broca's area, the region of the brain that helps people produce speech and found more blood flow in the area while patients were having auditory hallucinations.
"Hearing voices" most common. Affects 3/4 of schizophrenia patients. They hear sounds and voices that come from outside their head. They can talk directly to them sometimes giving commands or warnings, or they may be experienced as overheard.
-Illusions are distorted or misinterpreted real perceptions.
-Imagery is under voluntary control and doesn't mimic real perception.
-Dreaming occurs when a person is asleep.
-Failure to recognize internally generated speech as one's own. Cross-activtation with the auditory areas, so what most people experience as thoughts become "voiced".
-Abnormal attention to the subvocal stream that accompanies verbal thinking.
Prior to the 18th century, it was believed to be caused by supernatural forces such as Gods, demons, angels or djinns.
In the Middle of the 18th century, they were believed to be caused by the overactivity of certain centers in the brain.
They may smile when making a somber statement or upon being told terrible news, or they may become upset in situations that should make them happy.
They may also undergo inappropriate shifts in mood such as a romantic moment with a partner, then suddenly begin yelling obscenities at them.
These are "pathological deficits," characteristics that are LACKING in a person. Poverty of speech, blunted and flat affect, loss of volition, and social withdrawal are commonly found in schizophrenia.
Conversely, the front of the brain, which is responsible for determining the source of sounds, was quiet during the hallucinations.
A blunted/restricted affect—they show less anger, sadness, joy, and other feelings than most people and some show almost no emotions at all.
Apathy, feeling drained of energy and of interest in normal goals and unable to start or follow through on a course of action.
Many schizophrenia patients suffer from some form of this dysfunction. They can't track the slow moving target and rather than steadily track it, their eyes fall back and then catch up in a jerky movement.
Stupor, fixed rigid posturing, almost no movement or excitement. Can take on extreme forms.
They may become unaware of the environment and maintain a rigid/fixed posture (even bizarre) and seemingly strenuous positions for hours as their limbs become stiff or swollen.
The phases may last days or years, and a fuller recovery from schizophrenia is more likely in people who functioned well before the disorder (premorbid functioning) whose initial disorder is triggered by stress, comes on abruptly, or develops during middle age and who receive early treatment, preferably during prodromal phase.
In at least one of those months, the person must be in an active phase, marked by significant delusions, hallucinations, or disorganized speech.
In addition, there must be a deterioration in the person's work, social relations, and ability to care for themselves.
Patients generally seem to have been better adjusted prior to the disorder, to have later onset of symptoms, and to be more likely to show improvement, especially when treated with medications.
The symptoms are triggered by the enormous shift in hormone levels that takes place after delivery. Within days or few months of birth, the woman develops signs of losing touch with reality, such as delusions (ex: her baby is the devil) hallucinations (ex: hearing voices) extreme anxiety, confusion, and disorientation disturbed sleep and illogical or chaotic thoughts (ex: thoughts about killing herself or her child).
Certain neurons that use the neurotransmitter dopamine (particularly neurons in the striatum region of the brain) fire too often and transmit too many messages, thus producing the symptoms of schizophrenia.
Quells the more obvious symptoms such as hallucinations and delusions. Medications that help remove the symptoms of schizophrenia.
1st generation drugs are phenothiazines.
2nd generation drugs are atypical antipsychotics - that have the advantage of fewer neurological side effects and a lower risk of TD.
Drugs that help correct grossly confused or distorted thinking.
Some people with Parkinson's disease develop schizophrenia-like symptoms if they take too much L-dopa, a medication that raises Parkinson's patients' dopamine levels. The L-dopa apparently raises the dopamine activity so much that it produces psychosis.
Research on amphetamines - which stimulate the central nervous system. Investigators noticed in the 1970s that people who take high doses of amphetamines may develop amphetamine psychosis—a syndrome very similar to schizophrenia. They also found that antipsychotic drugs can reduce the symptoms of amphetamine psychosis, just as they reduce the symptoms of schizophrenia. Eventually researchers learned that amphetamines and similar stimulant drugs increase dopamine activity in the brain, thus producing schizophrenia-like symptoms.
Investigators located areas of the brain that are rich in dopamine receptors and have found that phenothiazines and other antipsychotic drugs bind to many of these receptors. The drugs are dopamine antagonists—drugs that bind to dopamine receptors, prevent dopamine from binding there, and so prevent the neurons from firing.
Excessive dopamine floods the brain, leading them to process stimulus information at too high a rate. They are unable to forget or disregard extraneous sensory information, which leads to a process dubbed "hyperlearning."
Researchers simulated the effects of a dopamine flood by programing the computer system to process information at a faster and faster rate, while at the same time programming it to ignore less and less data.
When it had finished being reprogrammed, it began to display patterns of functioning that were similar to those found in people with schizophrenia.
When dopamine carries a message to a receiving neuron, it must bind to a receptor on the neuron. A larger number of receptors or abnormal operation by the receptors could result in more dopamine binding and thus more neuron firing.
The drugs bind not only to D-2 dopamine receptors, like the traditional, or conventional, antipsychotic drugs, but also to many D-1 receptors and to receptors for other neurotransmitters such as serotonin.
Schizophrenia could be related to abnormal activity or interactions of both dopamine and serotonin and perhaps other neurotransmitters (ex: glutamate and GABA), rather than to abnormal dopamine activity alone.
2) Some theorists claim that excessive dopamine activity contributes primarily to the positive symptoms of schizophrenia such as delusions and hallucinations.
Positive symptoms respond well to the conventional antipsychotic drugs, which bind so strongly to D-2 receptors, whereas some of the negative symptoms (such as restricted affect and loss of volition) respond best to the second-generation antipsychotic drugs, which bind less strongly to D-2 receptors.
Some studies suggest they have smaller temporal and frontal lobes than other people, smaller amounts and cortical white and grey matter, and/or abnormal blood flow—either reduced or heightened—in certain areas of the brain.
2) Animal model investigations, found that an unusually large number of people with schizophrenia are born during the winter. The winter birth rate among people with schizophrenia is 5 to 8 percent higher than among other people. This could be because of an increase in fetal or infant exposure to viruses at that time of year.
3) Investigations of fingerprints. People with schizophrenia often have significantly more or fewer ridges than their nonschizophrenic identical twins. Fingerprints form in the fetus during the 2nd trimester, when the fetus is most vulnerable to certain viruses. The fingerprint irregularities of some people with schizophrenia could reflect a viral infection contracted during the prenatal period, an infection that also predisposed the individuals to schizophrenia.
4) Studies show mothers of schizophrenic children were more likely to have been exposed to the influenza virus during pregnancy than were mothers of people without schizophrenia.
She described the mothers of people who develop the disorder as cold, domineering, and uninterested in their children's needs. These mothers may appear to be self-sacrificing but are actually using their children to meet their own needs.
They propose that some people are not reinforced for their attention, proficiency and responding to social cues. As a result, they stop attending to cues and focus on irrelevant cues—the brightness of light in a room, a bird flying above, or the sound of a word rather than its meaning. As they attend more and more to irrelevant cues, their responses become increasingly bizarre. Because the bizarre responses are rewarded with attention or other types of reinforcement, they are likely to be repeated again and again.
They are more likely to recover from their disorder and less likely to have continuous or episodic symptoms, impaired social functioning, or to require heavy antipsychotic drugs or hospitalization.
The children cannot avoid displeasing their parents because nothing they do is right, so the symptoms of schizophrenia represent the child's attempt to deal with the double binds.
A child who is repeatedly exposed to double-bind communications will adopt a special life strategy for coping with them. Ex: Always ignore primary communications and respond only to metacommunications: be suspicious of what anyone is saying, wonder about its true meaning, and focus on clues only in gestures or tones. People who increasingly respond to messages in this way may progress toward paranoid schizophrenia.
Arguing that schizophrenia is actually a constructive process in which people try to cure themselves of the confusion and unhappiness caused by their social environment.
2. At least one of the individual's symptoms must be delusions, hallucinations, or disorganized speech.
3. Individual functions much more poorly in various life spheres than was the case prior to the symptoms.
2. Negative Symptoms: Deficits of thought, emotion and behaviour.
-Loss of volition
-Blunted with flat affect
They may feel their senses are being flooded by all the sights and sounds that surround them.
Some show almost no emotion at all - flat affect. Their faces are still, eye contact poor, voices monotonous - showing a "mask".
If they are confused with their personal identity they may fail to recognize themselves as unique individuals and be unclear about how much of what they experience is part of themselves.
They may fail to recognize themselves as unique individuals and be unclear about how much of what they experience is part of themselves.
Genes that play a role in brain development may be especially implicated.
Twins have received the most research.
-Studies of identical twins found that if one twin develops the disorder, there is a 48% chance that the other twin will develop it as well.
-Fraternal twins have a 17% chance of developing the disorder.
The closer the genetic relationship between schizophrenia patients and their family members, the greater the likelihood (concordance rate) that the relatives will also have schizophrenia.
The major source of evidence for the dopamine model is found in the effects of antipsychotic drugs called neuroleptics. This theory is based on the effectiveness of the medications.
Over past 4 decades, researchers developed this hypothesis to explain findings. Certain neurons using dopamine fire too often, producing symptoms of schizophrenia.
The medications were originally developed for treating allergies but found to cause a Parkinson's disease-like tremor response in patients. Scientists knew that Parkinson's patients had abnormally low dopamine levels, which caused their shaking. This relationship between symptoms suggested that symptoms of schizophrenia were related to excess dopamine.
-Ex: people with Parkinson's develop schizophrenic symptoms if they take too much L-dopa, a medication that raises dopamine levels.
-Ex: people who take high doses of amphetamines, which increase dopamine activity in the brain, may develop amphetamine psychosis - a syndrome similar to schizophrenia.
Researchers have located the dopamine receptors to which antipsychotic drugs bind - the drugs are apparently dopamine antagonists that bind to receptors, preventing dopamine from binding and the neuron from firing. This suggests that in schizophrenia, the messages travelling from dopamine-sending neurons to dopamine-receptors (D-2) may be transmitted to easily or too often. An appealing theory because certain dopamine receptors are known to play a key role in guiding attention.
What If I Have Too Little or Too Much Dopamine?
Dopamine dysregulation could mean that the brain is producing too little or too much dopamine. Low dopamine, or dopamine deficiency, can be caused by a variety of factors, including conditions such as Parkinson’s disease, schizophrenia, and depression. Drug and sugar addiction have also been found to cause dopamine deficiency over time. Some low dopamine symptoms include fatigue, moodiness, dysphoria, physical pain, and changes in weight, sex drive, and ability to focus. As many other conditions share these symptoms, it’s important to consult your health care provider if you’re experiencing these symptoms.
It’s also possible to have too much dopamine. Effects of overly high dopamine levels include high libido, anxiety, difficulty sleeping, increased energy, mania, stress, and improved ability to focus and learn, among others. When certain parts of the brain are exposed to too much dopamine, for instance right after an individual takes illicit drugs, other behaviors may be present. These can include aggression, hallucinations, twitching, nausea and/or vomiting, and depression.
How Are Marijuana & Dopamine Linked?
Dopamine is the chemical responsible for activating the pleasure centers in your brain. When you smoke marijuana in the short-term, have sex, or eat/drink something you love, the pleasure you feel is caused by heightened dopamine production. The reason why illicit drugs are so addictive is that they activate this pleasure pathway, and you become hooked on the sensation before you even know it.
Short-term marijuana use is known to increase dopamine in your brain indirectly. While the cannabinoids contained in weed don’t act on the dopamine neurons directly, they do act on the body’s endocannabinoid system (ECS) , which temporarily suppresses GABA inhibitors. GABA neurons are neurons that inhibit dopamine production – when they’re suppressed, dopamine production increases.
Endocannabinoids (the cannabinoids that are produced naturally by the body) play a huge role in our daily functions. A 2013 study by Dubreucq et al., for instance, looked at mice that had been born with no cannabinoid receptors. The researchers found that these mice used their exercise wheels up to 30% less often than healthy mice.
Signs of Dopamine Deficiency
The Merck Manual describes minor side effects of intravenous dopamine administration, which include:
- fast heart beat,
- irritation or skin necrosis at the site of injection 4
February 1997'). Patients, such as diabetics, with blood circulation problems or peripheral vascular disease are at an increased risk for dopamine gangrene.